Orthogonal synthesis of pyrroles and 1,2,3-triazoles from vinyl azides and 1,3-dicarbonyl compounds

Tri- and tetrasubstituted N-H pyrroles were prepared by the simple treatment of vinyl azides with 1,3-dicarbonyl compounds in toluene at 100 °C via 2H-azirine intermediates generated in situ. When the reactions of vinyl azides and 1,3-dicarbonyl compounds were performed in DMF in the presence of a catalytic amount of K₂CO₃, 1-vinyl-1,2,3-triazoles were obtained via 1,3-dipolar cycloaddition. These methodologies exploited orthogonal modes of chemical reactivity of vinyl azides, which could be achieved by slight modification of the reaction conditions.     

Mn(III)-catalyzed synthesis of pyrroles from vinyl azides and 1,3-dicarbonyl compounds

Polysubstituted N-H pyrroles with a wide variety of substituents were prepared from vinyl azides and 1,3-dicarbonyl compounds by using Mn(III) complexes as catalysts.     

Divergent reactivity of α-oximino carbenoids: facile access to 2-isoxazolines and 2H-azirines

Mild catalytic reaction conditions for the synthesis of 2-isoxazolines and 2H-azirines have been developed via carbenoids derived from α-oximino diazo compounds. This has been utilized in the one-pot synthesis of pyrroles in the presence of 1,3-dicarbonyl compounds.     

Regioselective synthesis of functionalized ferrocenylphenols based on cyclocondensation reactions of free and masked 1,3-dicarbonyl dianions

Highly functionalized ferrocenyl-substituted phenols were prepared by cyclization of masked or free dianions with 1,3-dielectrophilic 1-η5-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-ones. While the cyclizations of 1,3-bis(silyloxy)-1,3-butadienes (masked dianions) proceed by initial 1,2-addition, the reactions of free 1,3-dicarbonyl dianions proceed by initial 1,4-addition. Therefore, both regioisomeric ferrocenylphenols are available from one and the same electrophile dependent on the type of nucleophile and reaction conditions employed. The reactions reported represent the first examples of the application of formal [3 + 3] cyclizations to the synthesis of organometallic compounds.     

A combined experimental and theoretical study of the thermal cycloaddition of aryl azides with activated alkenes

Reactions were performed from aryl azides on the one hand, and activated alkenes coming from β-dicarbonyl compounds or malonodinitrile on the other hand, either with recourse to conventional heating or to microwave activation, to afford 1-aryl-1H-1,2,3-triazoles. The mechanism and the regioselectivity of the reactions involving β-dicarbonyl compounds have been theoretically studied using DFT methods at the B3LYP/6-31G* level: they are domino processes comprising a tautomeric equilibrium of the β-dicarbonyl compounds with their enol forms, a 1,3-dipolar cycloaddition of the enol forms with the aryl azides (high activation energy), and a dehydration process (lower activation energy). The effect of non-conventional activation methods on the degradation of 1,2,3-triazolines was next studied experimentally. Finally, some of the 1,2,3-triazoles such synthesized were evaluated for their bactericidal and cytotoxic activities.     

Synthesis of polysubstituted pyrroles via a gold(I)-catalyzed tandem three-component reaction at room temperature

A gold(I)-catalyzed three-component reaction of β-nitrostyrenes with 1,3-dicarbonyl compounds and primary amines to form polysubstituted pyrroles has been developed at room temperature in ethanol. The key advantages of the three-component reaction are the mild reaction conditions and environm entally safer solvent     

Formation of pyrroles from β-chloroazoalkenes and 1,3-dicarbonyl compounds

The azoalkenes (1) have been prepared from the corresponding hydrazones of dichloroacetalhyde; they react with 1,3-dicarbonyl compounds to give first the addition-elimination products (4) and then pyrroles (6).     

One-pot three-component catalytic synthesis of fully substituted pyrroles from readily available propargylic alcohols, 1,3-dicarbonyl compounds and primary amines

A simple and highly efficient method for the preparation of fully substituted pyrroles, from readily accessible secondary propargylic alcohols, 1,3-dicarbonyl compounds and primary amines, has been developed. The one-pot multicomponent reaction, which is catalysed by the system [Ru(eta(3)-2-C(3)H(4)Me)(CO)(dppf)][SbF(6)]/CF(3)CO(2)H (dppf: 1,1'-bis(diphenylphosphanyl)ferrocene), involves initial propargylation of the 1,3-dicarbonyl compound promoted by CF(3)CO(2)H and subsequent condensation between the resulting gamma-keto alkyne and the primary amine to afford a propargylated beta-enamino ester or ketone, which undergoes a ruthenium-catalysed 5-exo-dig annulation to form the final pyrrole.     

Promiscuous zinc-dependent acylase-mediated carbon-carbon bond formation in organic media

A zinc-dependent acylase, D-aminoacylase from Escherichia. Coli, displays a promiscuous activity to catalyze the carbon-carbon bond formation reaction of 1,3-dicarbonyl compounds to methyl vinyl ketone in organic media.     

Synthesis of polyfunctionalized pyrroles bearing C-2 α-azido side-chains and displacement of the α-azido group by various nucleophiles

Tetrasubstituted pyrroles bearing C-2 α-azido side-chains were synthesized employing a new class of diazides, α,γ-diazido α,β-unsaturated esters, and 1,3-dicarbonyl compounds under simple thermal conditions. Further investigation of the synthetic utility of the obtained pyrroles reveals unexpected displacement of the α-azido group at the C-2 side-chain by a variety of nucleophiles. This two-step process exhibits a broad substrate scope, good functional group tolerance, simple operation, and high reaction efficiency, providing an easy access to polyfunctional pyrroles with novel substitution patterns.     

Axially chiral guanidine as enantioselective base catalyst for 1,4-addition reaction of 1,3-dicarbonyl compounds with conjugated nitroalkenes

A new strategy for designing chiral guanidine molecules is presented, which features the introduction of an axially chiral binaphthyl backbone. The axially chiral guanidine catalysts thus developed facilitated the highly enantioselective 1,4-addition reaction of 1,3-dicarbonyl compounds with a broad range of conjugated nitroalkenes and showed extremely high catalytic activity.     

A convenient approach to the synthesis of 2-(2-aminoethyl)pyrroles and their heterocyclization into hydrogenated pyrrolopyridines and related pyrroloindolizines

2-(2-Aminoethyl)pyrroles and 2-(2-succinimidoethyl)pyrroles were prepared from acetals of ethyl 4-oxoalkanoates via latent vinyl 1,4-dicarbonyl compounds as the key intermediates. The Pictet-Spengler condensation of 2-(2-aminoethyl)pyrroles with aromatic aldehydes gave 4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridines in good yields. 4,5,7,8,9,9a-Hexahydro-3H-pyrrolo[2,3-g]indolizines were prepared in a similar way starting from 2-(2-succinimidoethyl)pyrroles.     

Zn(II)/amine-catalyzed coupling reaction of alkylidenemalonates with propargyl alcohol: a one-pot synthesis of methylenetetrahydrofurans

[reaction: see text] A metal-catalyzed tandem 1,4-addition/cyclization between propargyl alcohol and a Michael acceptor, such as alkylidene malonate, has been developed. In the presence of catalytic amounts of zinc triflate [Zn(OTf)(2)] and triethylamine (Et(3)N), various 2-alkylidene-1,3-dicarbonyl compounds reacted with propargyl alcohol to give 3- or 4-methylene tetrahydrofurans in excellent yields.     

Regioselective synthesis of 5-trifluoromethyl-1,2,3-triazoles via CF3-directed cyclization of 1-trifluoromethyl-1,3-dicarbonyl compounds with azides

1-Trifluoromethyl-substituted 1,3-dicarbonyl compounds are shown to undergo 100% regioselective cyclization in reactions with alkyl and aryl azides to form 4-acyl-5-trifluoromethyl-1,2,3-triazoles. The reaction represents a general method for the synthesis of otherwise difficulty available 4-acyl-5-trifluoromethyl-1,2,3-triazoles. The directing role of the trifluoromethyl group is discussed in the light of stepwise and concerted mechanisms for this reaction.     

Conversion of 1,3- into 1,4-dicarbonyl compounds by means of α-phosphoryl sulphides. Total synthesis of dihydrojasmone and methylenomycin B.

An effective synthesis of 1,4-dicarbonyl systems involving the Horner—Wittig reaction of α-phosphoryl sulphides with the half-protected 1,3-dicarbonyl compounds followed by hydrolysis of the vinyl sulphides formed is described. The total synthesis of dihydrojasmone and methylenomycin B employing this approach is reported.     

CuI/L-proline-catalyzed coupling reactions of aryl halides with activated methylene compounds

[reaction: see text] The arylation of ethyl acetoacetate, ethyl benzoyl acetate, and diethyl malonate under the catalysis of CuI/L-proline in DMSO proceeds smoothly at 40-50 degrees C in the presence of Cs2CO3 to provide the 2-aryl-1,3-dicarbonyl compounds in good yields. Both aryl iodides and aryl bromides are compatible with these reaction conditions.     

Potassium fluoride-promoted reaction of (2-chloro-2-nitroethenyl)benzenes with 1,3-dicarbonyl compounds. A general synthesis of 6,6-dimethyl-2-nitro-3-phenyl-3,5,6,7-tetrahydro-4(2H)benzofuranones and some analogs

A convenient procedure to prepare in good yields 6,6-dimethyl-2-nitro-3-phenyl-3,5,6,7-tetrahydro-4(2H)-benzofuranones starting from (2-chloro-2-nitroethenyl)benzenes and 5,5-dimethyl-1,3-cyclohexanedione in the presence of potassium fluoride is reported. This method also proved efficient with other 1,3-dicarbonyl compounds, and has been successfully extended to 1,3-cyclohexanedione, 2,5-pentanedione, dibenzoylmethane and ethyl acetoacetate.     

Three-Component Coupling Synthesis of Diversely Substituted N-Aryl Pyrroles Catalyzed by Iron(III) Chloride

An efficient and operationally simple three-component coupling synthesis of varieties of N-aryl substituted pyrroles is described in the presence of sustainable and environmentally benign metal catalyst, FeCl₃. This method provides a straightforward approach for the synthesis of N-aryl substituted pyrroles in good yields from easily accessible starting materials such as nitroalkenes, 1,3-dicarbonyl compounds, and primary aromatic amines. The reaction proceeds through a catalytic sequence of Fe(III)-catalyzed amination/Michael/cycloisomerization reactions.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Approach to Synthesis of β-Enamino Ketones and Pyrroles Catalyzed by Gallium(III) Triflate Under Solvent-Free Conditions

Metal triflates have been used to catalyze synthesis of β-enamino ketones or pyrroles from amines and 1,3-dicarbonyl or 1,4-dicarbonyl compounds under solvent-free conditions, respectively. Among different metal triflates screened, 0.5 mol% Ga(OTf)₃ efficiently promoted the reactions to give excellent yields. In addition, the catalyst could be recovered easily after the reactions and reused without evident loss in activity.     

Silver-mediated oxidative C-H/C-H functionalization: a strategy to construct polysubstituted furans

A novel silver-mediated highly selective oxidative C-H/C-H functionalization of 1,3-dicarbonyl compounds with terminal alkynes for the creation of polysubstituted furans and pyrroles in one step has been demonstrated. Promoted by the crucial silver species, perfect selectivity and good to excellent yields could be achieved. This protocol represents an extremely simple and atom-economic way to construct polysubstituted furans and pyrroles from basic starting materials under mild conditions.